Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53
Summary: Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and M...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723014900 |
| _version_ | 1827673911597203456 |
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| author | Jonathan D. Lee Bridget L. Menasche Maria Mavrikaki Madison M. Uyemura Su Min Hong Nina Kozlova Jin Wei Mia M. Alfajaro Renata B. Filler Arne Müller Tanvi Saxena Ryan R. Posey Priscilla Cheung Taru Muranen Yujing J. Heng Joao A. Paulo Craig B. Wilen Frank J. Slack |
| author_facet | Jonathan D. Lee Bridget L. Menasche Maria Mavrikaki Madison M. Uyemura Su Min Hong Nina Kozlova Jin Wei Mia M. Alfajaro Renata B. Filler Arne Müller Tanvi Saxena Ryan R. Posey Priscilla Cheung Taru Muranen Yujing J. Heng Joao A. Paulo Craig B. Wilen Frank J. Slack |
| author_sort | Jonathan D. Lee |
| collection | DOAJ |
| description | Summary: Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants. |
| first_indexed | 2024-03-10T04:31:22Z |
| format | Article |
| id | doaj.art-fc5e40c8967549f19441624446c62419 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-10T04:31:22Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fc5e40c8967549f19441624446c624192023-11-23T04:28:16ZengElsevierCell Reports2211-12472023-12-014212113478Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53Jonathan D. Lee0Bridget L. Menasche1Maria Mavrikaki2Madison M. Uyemura3Su Min Hong4Nina Kozlova5Jin Wei6Mia M. Alfajaro7Renata B. Filler8Arne Müller9Tanvi Saxena10Ryan R. Posey11Priscilla Cheung12Taru Muranen13Yujing J. Heng14Joao A. Paulo15Craig B. Wilen16Frank J. Slack17Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Corresponding authorDepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USAStem Cell Program, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USADepartment of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USADepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02115, USA; Corresponding authorSummary: Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.http://www.sciencedirect.com/science/article/pii/S2211124723014900CP: Immunology |
| spellingShingle | Jonathan D. Lee Bridget L. Menasche Maria Mavrikaki Madison M. Uyemura Su Min Hong Nina Kozlova Jin Wei Mia M. Alfajaro Renata B. Filler Arne Müller Tanvi Saxena Ryan R. Posey Priscilla Cheung Taru Muranen Yujing J. Heng Joao A. Paulo Craig B. Wilen Frank J. Slack Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 Cell Reports CP: Immunology |
| title | Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 |
| title_full | Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 |
| title_fullStr | Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 |
| title_full_unstemmed | Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 |
| title_short | Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53 |
| title_sort | differences in syncytia formation by sars cov 2 variants modify host chromatin accessibility and cellular senescence via tp53 |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723014900 |
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